Effect of Rosuvastatin on Endothelial Function

Phase 2

Terminated

Brief Summary: Rosuvastatin belongs to a class of medications commonly called "statins" which are medications given for high low density lipoprotein (LDL) 'bad' cholesterol to prevent atherosclerosis (hardening of blood vessels) and lower risk of heart attacks and other circulation problems. Recent studies in the general non-HIV infected population have shown that the beneficial effect of statins in preventing circulation problems is larger than would be expected from lowering of LDL-cholesterol alone. It has been suggested that the additional beneficial effect of statins may be due to the anti-inflammatory effect of statins.

The risk of heart attacks and other circulation problems may be high in HIV infected individuals. This may be due to the inflammatory stress effects of HIV. The main purpose of the study is to see if rosuvastatin will have a beneficial effect on the circulatory system in HIV infected individuals even in those who do not have high LDL cholesterol levels. Therefore, in HIV-infected individuals with normal or low LDL cholesterol levels but with evidence of low HDL cholesterol levels which may be a sign of low grade inflammation, the study will look at whether 3 months of rosuvastatin will lead to improvement in brachial artery flow-mediated dilatation (FMD), a marker of early atherosclerosis (hardening of the blood vessels).

Recruitment & Eligibility

Inclusion Criteria

HIV infection
Age > 18 years old
On stable antiretroviral therapy for > 6 months with no plans to change therapy during the treatment phase of the study
Plasma HIV RNA < 50 copies/mL
Karnofsky performance score > 70 within 30 days prior to study entry
Ability to understand and sign informed consent
Following laboratory values obtained within 30 days prior to randomization:
- Absolute neutrophil count (ANC) > 750/mm3
- Hemoglobin >/= 8.0 g/dL
- Platelets >/= 50,000/mm3
- ALT (SGPT) and AST (SGOT) < 2.5 x ULN
- Fasting glucose < 126 mg/dL
- TSH < 3.0 mIU/L
HDL-C < 50 mg/dL in men, < 55 mg/dL in women
Direct LDL-C </= 130 mg/dL
Calculated creatinine clearance > 50 mL/min
Willing to be treated with rosuvastatin or be on an observational arm for a minimum of 3 months
Female subject must not participate in a conception process (active attempt to become pregnant) or be post-menopausal. If participating in sexual activity that could lead to pregnancy, the subject must use contraception while receiving study medication and 30 days after stopping the medication

Exclusion criteria

History of past cardiovascular event
Acute illnesses or active AIDS-defining opportunistic infection (OI) within 30 days prior to entry
Other chronic illness including diabetes, autoimmune diseases, and endocrinopathies
Serology positive for hepatitis B surface antigen or hepatitis C antibody
Signs and symptoms of liver failure
Receipt of supraphysiologic glucocorticoid therapy within 3 months prior to study entry
Use of lipid lowering agents within 30 days prior to study entry
Receipt of an HIV vaccine or investigational agents
Pregnancy or breast-feeding
Presence of any active malignancy within the last 5 years
Severe Hypertension (Systolic >/= 180 or Diastolic >/= 110 mm Hg)
Use of oral postmenopausal hormone replacement therapy
Known hypersensitivity to rosuvastatin
Active drug or alcohol dependence
Any acute illness within 30 days prior to study entry that, in the opinion of the site investigator, would interfere with participation in the study.
Use of lopinavir/ritonavir (Kaletra) as part of current HIV antiretroviral regimen

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
rosuvastatin	rosuvastatin	rosuvastatin 10 mg qd increased to 20 mg qd as tolerated

Primary Outcome Measures

Name	Time	Method
Change in Flow Mediated Dilatation (FMD) of the Brachial Artery	3 months

Secondary Outcome Measures

Name	Time	Method
Change in Glucose Homeostasis and Insulin Resistance as Assessed by Oral Glucose Tolerance Testing	3 months
Change in hsCRP	3 months
Change in HIV Biomarkers of Immune Activation to Include CD38 and CD69 Expression on T Cells and CD16 and CD69 Expression on Monocytes	3 months
Change in Mitochondrial-specific Oxidative Stress (Mt-specific 8-oxo-dG) and Oxidative Phosphorylation (OXPHOS) Protein/Enzyme Activity [Complex I and Complex IV] Levels	3 months
Change in Total, HDL and LDL Cholesterol and Triglyceride Levels	3 months